Treatment with 4 months of rifampin (4R) for latent tuberculosis (TB) infection was associated with substantially higher adherence, lower costs, and lower risk for severe hepatoxicity compared with 9 months of isoniazid (9H), according to study results published in the European Respiratory Journal.

In this retrospective cohort study, researchers identified 10,559 patients who initiated treatment for latent TB infection between 2003 and 2007 in Quebec, Canada. The main exposure variable was whether the patient started treatment with isoniazid (n=9684) or rifampin (n=875). Hepatotoxicity was assessed from hospitalization records, adherence to treatment regimen was estimated from community pharmacy records, and per-patient costs were calculated from billing records and fee schedules.

The risk for severe hepatic adverse events was higher in the 9H group than in the 4R group (15 vs 1; adjusted odds ratio, 2.3; 95% CI, 0.3-16.1). Patients with no comorbidities had the lowest hepatotoxicity risk. Treatment completion was higher for patients in the 4R group than in the 9H group (53.5% vs 36.9%; respectively; adjusted risk ratio, 1.5; 95% CI, 1.3-1.7). After adjusting for age and comorbidities, the mean per-patient costs during latent TB infection treatment were lower for 4R patients than for 9H patients (adjusted cost ratio, 0.7; 95% CI, 0.5-0.9).

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This study was limited by missing inpatient drug dispensation data that were only available from community-based pharmacies, which could have led to underestimation of drug costs and latent TB infection treatment completion. In addition, the researchers relied on hospitalization data to identify patients with severe hepatotoxicity, so mild toxicity that did not result in hospitalization could not be accurately identified. Other potential adverse events associated with these regimens were not captured due to the limited analysis of hepatotoxic adverse events. There was potential confounding by indication as well as possible misclassification error due to inaccurate data.

“[O]ur results support previous findings that [latent TB infection] treatment for people aged 35 years and older without co-morbidities may be safe with appropriate liver function and symptom monitoring,” concluded the researchers. “[W]e believe this data strongly complements evidence from randomized trials; the similar results confirm the critically important safety advantage of rifampin compared [with] isoniazid-based treatment.”


Ronald LA, FitzGerald JM, Bartlett-Esquilant G, et al. Treatment with isoniazid or rifampin for latent tuberculosis infection: population-based study of hepatotoxicity, completion, and costs [published online January 24, 2020]. Eur Respir J. doi:10.1183/13993003.02048-2019